Possible Interaction: Fenclonine and Phenylalanine

“Hyperphnylalaninemia (experimental PKU) induced in developing rats by treatment with p-chlorophenylalanine (PCPA) plus phenylalanine (PHE) causes a significant reduction in the triphosphoinositide (TPI) and diphosphoinositide (DPI) content of brain.”

“The more than 50 ~ deficit in body weight (as well as the high rate of mortality) caused by the treatment with p-chlorophenylalanine plus phenylalanine is another factor which renders these animals unsuitable for most behavioral studies.”

“Experimental maternal hyperphenylalaninemia produced in pregnant F344 rats by the combined use of p-Chloro-DL-phenylalanine and L-phenylalanine reduced fetal birth weight in comparison to saline-injected controls.”

“In rats injected with p-chlorophenylalanine every 48h and with phenylalanine every 24h from 3 to 18 days of age, the hepatic and renal phenylalanine hydroxylase remained inhibited, whereas the activities of three other hepatic enzymes were unchanged.”

“Rats treated with p-chloro-DL-phenylalanine plus L-phenylalanine during the vulnerable period of rapid brain development thus have enduring behavioral changes that persist throughout life.”

“As with the rat enzyme, human phenylalanine hydroxylase acted also on p-fluorophenylalanine, which was inhibitory at high concentrations, and p-chlorophenylalanine acted as an inhibitor competing with phenylalanine.”

“ para-Chlorophenylalanine , which inhibits the enzyme that converts phenylalanine to tyrosine, was used to induce hyperphenylalaninemia during brain development in mice.”

“The activity of acid DNase was reduced in both cerebellum and cerebrum from 11 as well as 21 day old rats treated with PCPA plus PHE , but the enzyme activity was not altered in the tissues from rats of both ages treated with αMPA plus PHE.”

“The results showed that the DNA content of cerebellum as well as cerebrum was reduced by treatment with PCPA plus PHE , while treatment with αMPA plus PHE had no effect on DNA content in cerebellum but reduced the levels in cerebrum.”

“The turnover (degradation) of DNA was increased in both cerebellum and cerebrum from rats treated with PCPA plus PHE but αMPA plus PHE treatment did not alter the DNA turnover either in cerebellu or in cerebrum.”

“This suggests that treatment of rats with PCPA plus PHE during suckling inhibits cell proliferation and/or increases naturally occurring cell death in both cerebellum and cerebrum while treatment with αMPA plus PHE inhibits only cell proliferation and in cerebrum alone.”

“… PCPA … PHE the reduction in cerebral DNA levels occurs due to reduced synthesis and/or increased turnover (degradation) of DNA but that the reduction in cerebellar … increased turnover (degradation), and that in rats treated with αMPA plus PHE the reduction in cerebral DNA must occur due to reduced synthesis.”

“The hydroxylation of phenylalanine was inhibited by the addition of p-chlorophenylalanine and α-methyltyrosine, which are specific inhibitors of phenylalanine hydroxylase and tyrosine hydroxylase, respectively.”

“The hyperphenylalaninemia was induced by treatment with phenylalanine plus p-chlorophenylalanine.”